The long-term goal of this proposal is to understand how sensory circuits in the brain extract behaviorally relevant cues from information contained within a timing code. The timing of stimuli carries information in almost every sensory modality. For example, the timing cues of sounds are critical for aspects of human speech perception such as pitch and phoneme discrimination. Further, timing patterns may also play a role in a phenomenon called novelty detection, or the identification of a new sensory stimulus. Disruptions in the auditory processing of timing and novelty cues have been implicated in dyslexia, Central Auditory Processing Disorder, and autism. In audition and electrosensation, the decoding of timing cues is performed by midbrain neurons tuned to the time intervals between successive stimuli. Additionally, single-neuron novelty detectors have been found in mammalian auditory and fish electrosensory pathways. Several hypotheses attempt to describe how neural circuits can establish interval tuning and novelty detection, but the underlying behaviors of excitation and inhibition central to these hypotheses remain uncertain. Using a combination of cutting-edge electrophysiological and computational methods, this proposal will identify the interactions of excitatory and inhibitory inputs that produce interval tuning and novelty detection in electrosensory midbrain neurons of weakly electric fish. Aim 1 will determine the role of short-term synaptic plasticity of excitation and inhibition in establishing interval tuning. In vivo whole-cell patch clamp recordings during sensory stimulation with varying interstimulus intervals will be collected at different levels of current injection. Next, the excittory and inhibitory synaptic conductances underlying each neuron's responses will be calculated to reveal how short-term depression and/or facilitation contribute to producing interval tuning. Finally, the time constant and strength of plasticity of excitatory and inhibitory inputs onto mode leaky integrate-and-fire neurons will be varied and the response of the model neurons to varying-interval stimulation measured. These methods will test the hypothesis that interval tuning can result from differences in the time course of depression of excitatory and inhibitory pathways. Aim 2 will determine the role of short-term synaptic plasticity in detecting novel stimuli. The electrophysiological and computational methods employed in Aim 1 will be used to reveal the behavior of excitation and inhibition when a neuron is presented with a stimulus train consisting of common (more frequent) and rare (less frequent) stimulus pulses. The effect of varying the time courses of plastic excitation and inhibition onto model leaky integrate-and-fire neurons in response to the same stimuli will be measured. These methods will test the hypothesis that a subset of neurons that experience short-term depression of excitation will be able to detect novel stimuli. The results of this proposal will provide a description of the synaptc mechanisms employed by central circuits for the processing of timing information in a social communication pathway as well as further our understanding of the neural basis of several disorders. PUBLIC HEALTH RELEVANCE: This project holds relevance for understanding fundamental neural processes involved in sensory processing, and may provide insight into the dysfunction of neural circuits in conditions such as dyslexia, Central Auditory Processing Disorder, autism, and schizophrenia. A thorough knowledge of how intact neural pathways perform operations critical for sensory perception is vital to research that seeks to identify the underlying causes o complex human disorders.